Search Results (1,400)

Belatacept, a selective costimulation blocker targeting the CD28–CD80/86 pathway, represents a major innovation in solid organ transplantation immunosuppression. By providing upstream inhibition of T-cell activation without calcineurin inhibition, belatacept offers the potential for improved long-term graft and patient outcomes with reduced nephrotoxicity and metabolic adverse effects. This review summarizes the mechanistic rationale, pivotal evidence, and clinical experience supporting the use of belatacept as first-line or conversion therapy in solid organ transplantation, while addressing safety, pharmacoeconomic impact, and future research directions. A comprehensive analysis of pivotal phase II–III trials (BENEFIT, BENEFIT-EXT), recent prospective conversion studies, and ongoing trials in liver, heart, and lung transplantation was performed. Safety data and health–economic evaluations were critically appraised. In kidney transplantation, belatacept-based immunosuppression provides superior renal function and improved metabolic profiles compared with calcineurin inhibitors (CNIs), though with higher early acute rejection rates. In liver, heart, and lung transplantation, evidence remains limited, with de novo use contraindicated in liver grafts due to excess mortality and rejection. Conversion from CNI to belatacept in selected patients improves renal outcomes without compromising graft survival. Safety considerations include a higher risk of post-transplant lymphoproliferative disorder (PTLD) in Epstein–Barr virus-negative recipients. Belatacept represents a paradigm shift in transplant immunology by targeting upstream T-cell activation. While currently approved only for kidney transplantation, ongoing studies in thoracic and hepatic grafts may expand its therapeutic role. Personalized patient selection, combination regimens mitigating rejection risk, and real-world cost-effectiveness analyses will define its place in future precision immunosuppression strategies. Full article

Liver fibrosis induced by Schistosoma japonicum Katsurada, 1904 (S. japonicum) infection lacks effective diagnostic markers and specific anti-fibrotic therapies. Although dysregulated iron homeostasis and ferroptosis pathways may contribute to its pathogenesis, the core regulatory mechanisms remain elusive. To unravel the ferroptosis-related molecular features, this study integrated transcriptomic datasets (GSE25713 and GSE59276) from S. japonicum-infected mouse livers. Following batch effect correction and normalization, ferroptosis-related differentially expressed genes (FRDEGs) were identified. Subsequently, core hub genes were screened through the construction of a protein–protein interaction (PPI) network, functional enrichment analysis, immune infiltration evaluation, and receiver operating characteristic (ROC) analysis. The expression patterns of these hub genes were further validated in an S. japonicum-infected mouse model using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The study identified 7 hub genes (Lcn2, Timp1, Cth, Cp, Hmox1, Cbs, and Gclc) as key regulatory molecules. Functional enrichment analysis revealed that these hub genes are closely associated with sulfur amino acid metabolism and oxidative stress responses. Specifically, key enzymes involved in cysteine and glutathione (GSH) synthesis (Cth, Cbs, Gclc) were consistently downregulated, suggesting a severe impairment of the host antioxidant defense capacity. Conversely, pro-fibrotic and pro-inflammatory markers (Timp1, Lcn2, Hmox1) were upregulated. This molecular pattern was significantly associated with a remodeled immune microenvironment, characterized by increased infiltration of neutrophils and eosinophils. In vivo validation confirmed the expression trends of 6 hub genes, corroborating the bioinformatics predictions, while the discrepancy in Cp expression highlighted the complexity of post-transcriptional regulation in vivo. The identified hub genes demonstrated excellent diagnostic potential, with Timp1 achieving an area under the curve (AUC) of 1.000. This study elucidates the molecular link between S. japonicum infection and the ferroptosis pathway, suggesting that these hub genes may drive liver fibrosis progression by regulating sulfur metabolism and the immune microenvironment. These findings offer potential diagnostic biomarkers and novel therapeutic targets for schistosomal liver fibrosis. Full article

The tightly controlled and transient acquisition of a motile phenotype by otherwise static epithelial cells (epithelial–mesenchymal transition, EMT) enables the repair of a damaged epithelium. Conversely, a persistent, dysregulated, and exacerbated EMT characterizes epithelial malignancies such as breast carcinoma (BC) and oral squamous cell carcinoma (OSCC), being key for their metastasis and for their escaping anti-tumor immune responses. Herein, we investigated the relationship between EMT signatures and immune cell infiltration across OSCC and metastatic BC with the aim to identify prognostic markers and/or therapeutic targets common to both these malignancies, or unique to OSCC or BC. To this end, we analyzed publicly available transcriptomic datasets to identify coding genes involved in EMT with strong correlation to immune cell signatures. The methodology consisted of data selection, correlation analysis, signature overlap determination, and validation using independent databases. Results indicated that in both OSCC and BC the expression of EMT-related genes is strongly associated with that of immunosuppressive and pro-tumor macrophages. Notably, the FN1 gene coding for the extracellular matrix glycoprotein fibronectin (FN) emerged as the EMT gene common to either tumor types. In confirmation of this, FN protein levels were higher in OSCC and BC tissues than in their normal counterparts. Given FN capability of favoring tumor invasion and metastasis while hindering antitumor immune responses, these data encourage the development of FN antagonists to be used as an adjunct to conventional therapy in the treatment of both OSCC and BC. Full article

HTLV-1 and HIV-1 represent biologically significant, structurally close, and equally problematic yet divergent human retroviruses. Although both infect CD4+ T cells and share similar structural elements, they differ markedly in genomic stability, transmission dynamics, clinical progression, and, most importantly, their transcriptional regulatory mechanisms. HTLV-1, an ancient virus with a limited global burden, often remains asymptomatic for decades before potentially causing ATL or HAM/TSP. Conversely, HIV-1, a relatively recent zoonotic transmission, undergoes rapid replication, exhibits high genetic diversity, and causes progressive immunodeficiency unless controlled by antiretroviral therapy (ART). At the molecular level, HTLV-1 maintains proviral latency through a balanced bidirectional transcription of regulatory genes (e.g., Tax and HBZ) that manipulate host transcription and immune evasion pathways, facilitating persistence and oncogenesis. HBZ and Tax were shown to contribute to driving the progressive acquisition of Treg-like and HLA class II phenotype in chronically activated CD4+ T-cells, promoting tolerogenic antigen presentation and immune evasion in ATL cells. This well-controlled differential expression of HTLV-1 regulatory genes is attributed to multiple intragenic virus regulatory mechanisms, which will be discussed in this review. In contrast, HIV-1 transcription is driven by a tightly regulated 5′ LTR promoter involving host factors such as NF-κB, Sp1, AP-1, and NFAT, among others, with strong influence imposed by the landscape of the provirus integration site, playing a pivotal role in latency and reactivation. The distinct regulatory circuitry of each virus suggests a key difference in their essential regulation, with HTLV-1 primarily relying on intragenic mechanisms, while HIV-1 relies more heavily on interactions with the surrounding host environment to control its expression. This difference underscores unique therapeutic challenges in managing viral latency, persistence, and pathogenesis. Full article

Background/Objectives: Endocrine therapy (ET) is a common treatment for hormone-dependent breast cancer and is associated with a significant reduction in recurrence and mortality rates. However, the decision to initiate endocrine therapy is a critical and often distressing juncture for patients. The need to weigh its survival benefits against the potential burden of side effects, including mood changes, pain, muscle stiffness, and fatigue, can render this decision-making phase a source of significant distress. The present systematic review aimed to identify and synthesize the sociodemographic and psychosocial predictors of the decision-making process related to ET adherence among women with breast cancer. Methods: A systematic literature search was conducted in three electronic databases—PubMed Central, ProQuest, and Scopus—to identify studies examining the association between sociodemographic and psychosocial factors and the decision-making process regarding ET among women with breast cancer. Inclusion criteria encompassed cross-sectional studies published between 2000 and 2025. Data were extracted and analyzed to identify recurring predictors across studies. The findings were synthesized through a narrative synthesis. Results: Twelve cross-sectional studies met the inclusion criteria, comprising a total of 8510 women diagnosed with breast cancer and undergoing ET. Ten studies (83%) identified sociodemographic variables—such as age, marital status, educational level, and ethnicity—as significant predictors of decision-making. Moreover, nine studies (75%) reported psychosocial factors, including quality of life (QoL), fear of progression, infertility concerns, and social support, as influential in the decision to initiate or continue ET. Specifically, the decision to adhere to ET is generally supported by younger age, higher education, better perceived quality of life, and greater social support. Conversely, it is hindered by lower income, lower education, fertility concerns related to marital status, and diminished quality of life. Conclusions: The findings of this review indicate that both sociodemographic and psychosocial factors play key roles in shaping women’s decisions regarding adherence to ET. Understanding these predictors can facilitate decision-making and inform the development of targeted interventions aimed at improving treatment adherence and supporting patient-centered care in breast cancer treatment. The focus on decision-making processes, rather than on adherence rates, is what distinguishes this review from other systematic reviews. Full article

Mesenchymal stromal cells (MSCs) are intensively investigated in oncology owing to their intrinsic tumor-homing ability and capacity to deliver therapeutic agents directly into the tumor microenvironment (TME). Recent advances in genetic engineering have enabled precise modification of MSCs, allowing controlled expression of therapeutic genes and other cargo delivery, thus improving targeting efficiency. As cellular carriers, MSCs have been engineered to transport oncolytic viruses, suicide genes in gene-directed enzyme prodrug therapy (GDEPT), multifunctional nanoparticles, and therapeutic factors such as IFN-β or TRAIL, while engineered MSC-derived extracellular vesicles (MSC-EVs) offer a promising cell-free alternative. These strategies increase intratumoral drug concentration, amplify bystander effects, and synergize with standard therapies while reducing systemic toxicity. Conversely, accumulating evidence highlights the tumor-promoting properties of MSCs: once recruited by inflammatory and hypoxic cues, they remodel the tumor microenvironment by stimulating angiogenesis, suppressing immune responses, differentiating into cancer-associated fibroblasts, and promoting epithelial-to-mesenchymal transition (EMT), ultimately enhancing invasion, metastasis, and therapy resistance. This duality has sparked both enthusiasm and concern in the oncology field. The present review outlines the paradoxical role of MSCs in oncology—ranging from their potential to promote tumor growth to their emerging utility as vehicles for targeted drug delivery. By highlighting both therapeutic opportunities and biological risks, we aim to provide a balanced perspective on how MSC-based strategies might be refined, optimized, and safely integrated into future cancer therapies. Full article

Objectives: Peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NETs) commonly relies on somatostatin receptor subtype 2 (SSTR2) agonists such as DOTA-TOC/TATE, which may show limited efficacy due to high hepatic uptake and therapy resistance in some patients. SSTR2 antagonists have demonstrated superior tumor targeting. This study aimed to establish the production and quality control of the Actinium-225-labeled SSTR2 antagonist [²²⁵Ac]Ac-DOTA-LM3 and to report in-human clinical experience with targeted alpha therapy (TAT). Methods: [²²⁵Ac]Ac-DOTA-LM3 was produced by radiolabeling DOTA-LM3 with Actinium-225 under validated conditions. Radiochemical conversion, purity, yield, and stability were assessed using radio-TLC, fractionated radio-HPLC combined with gamma spectroscopy, and in vitro serum stability testing. Clinical feasibility and therapeutic response were evaluated in a patient with metastatic neuroendocrine pancreatic neoplasm refractory to prior ¹⁷⁷Lu-based PRRT. Results: Radiolabeling achieved reproducibly high radiochemical purity (>97%) and decay-corrected yields exceeding 80%. The radiopharmaceutical showed high in vitro stability with minimal release of free Actinium-225 over five days. Fractionated radio-HPLC enabled indirect purity assessment. In the reported patient, [²²⁵Ac]Ac-DOTA-LM3 therapy resulted in partial remission without clinically relevant hematologic, renal, or hepatic toxicity and was associated with marked clinical improvement. Conclusions: [²²⁵Ac]Ac-DOTA-LM3 can be produced with high purity and stability using clinically applicable procedures. In-human results suggest promising efficacy and safety, supporting further clinical investigation of Actinium-225-labeled SSTR2 antagonists for advanced NETs. Full article

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited treatment options for patients with locally advanced or metastatic disease. Endoscopic ultrasound (EUS)-guided intra-tumoral radioactive implantation has emerged as a minimally invasive approach to enhance local tumor control while minimizing systemic toxicity. Among the available isotopes, phosphorus-32 (³²P) microparticle brachytherapy has demonstrated promising outcomes, including significant tumor regression, reductions in CA 19-9, and higher rates of tumor downstaging and surgical conversion when combined with systemic chemotherapy. Compared with stereotactic body radiotherapy (SBRT), ³²P delivers higher intratumoral radiation doses, spares adjacent healthy tissues, and can be administered during ongoing chemotherapy without treatment interruption. Additionally, preliminary evidence suggests that ³²P may modulate the tumor microenvironment, improving vascularity and enhancing chemotherapy efficacy. The procedure shows high technical success and a favorable safety profile, with minimal serious adverse events. Future directions include prospective randomized trials to validate its impact on survival, optimize dosing, and establish treatment protocols. EUS-guided intra-tumoral ³²P brachytherapy holds potential as a key component of multimodal therapy, bridging local tumor control and systemic disease management in PDAC. Full article

Background: Colorectal cancer (CRC) demonstrates substantial clinical and biological diversity across age groups, ancestral backgrounds, and treatment settings, alongside a rising incidence of early-onset disease (EOCRC). The mitogen-activated protein kinase (MAPK) pathway is a major driver of CRC development and therapy response; however, the distribution and prognostic value of MAPK alterations across distinct patient subgroups remain unclear. Methods: We analyzed 2515 CRC tumors with harmonized demographic, clinical, genomic, and treatment metadata. Patients were stratified by ancestry (Hispanic/Latino [H/L] vs. non-Hispanic White [NHW]), age at diagnosis (early-onset [EO] vs. late-onset [LO]), and FOLFOX chemotherapy exposure. MAPK pathway alterations were identified using a curated gene set encompassing canonical EGFR-RAS-RAF-MEK-ERK signaling components and regulatory nodes. Conversational artificial intelligence (AI-HOPE and AI-HOPE-MAPK) enabled natural language-driven cohort construction and exploratory analytics; findings were validated using Fisher’s exact testing, chi-square analyses, and Kaplan–Meier survival estimates. Results: MAPK pathway disruption demonstrated marked heterogeneity across ancestry and treatment contexts. Among EO H/L patients, FGFR3, NF1, and RPS6KA6 mutations were significantly enriched in tumors not receiving FOLFOX, whereas PDGFRB alterations were more frequent in FOLFOX-treated EO H/L tumors relative to EO NHW counterparts. In late-onset H/L disease, NTRK2 and PDGFRB mutations were more common in non-FOLFOX tumors. Distinct MAPK-associated alterations were also observed among NHW patients, particularly in non-FOLFOX settings, including AKT3, FGF4, RRAS2, CRKL, DUSP4, JUN, MAPK1, RRAS, and SOS1. Survival analyses provided borderline evidence that MAPK alterations may be linked to improved overall survival in treated EO NHW patients. Conversational AI markedly accelerated analytic throughput and multi-parameter discovery. Conclusions: Although MAPK alterations are pervasive in CRC, their distribution varies meaningfully by ancestry, age, and treatment exposure. These findings highlight NF1, MAPK3, RPS6KA4, and PDGFRB as potential biomarkers in EOCRC and H/L patients, supporting the need for ancestry-aware precision oncology approaches. Full article

Immunotherapy, especially immune checkpoint inhibitors (ICIs), has become one of the core therapeutic approaches in cancer in recent years. It demonstrates remarkable efficacy in the treatment of melanoma and lung cancer. Conversely, its use in treating gastric cancer (GC) is not associated with considerable benefits. The high heterogeneity of GC and the tumor microenvironment (TME) may directly influence this phenomenon. This review focuses on the correlation between Helicobacter pylori (H. pylori) infection, gastric physiology, and molecular subtype-specific induction pathways, with emphasis on the unique metabolic features of GC. It explores the connection of H. pylori infection, gastric physiologic functions, and molecular subtype-specific induction mechanism of GC with the special metabolism of GC. It also explains the relationship between immune metabolic reprogramming and the suppressive TME in GC. Crucially, we summarize emerging therapeutic strategies targeting metabolic vulnerabilities. Furthermore, we explore the potential of subtype-guided metabolic therapies to overcome the challenges of the immunosuppressive tumor microenvironment in GC. Full article

This study aimed to provide a synthesis of current knowledge on iron homeostasis, focusing on major metabolic pathways and evolving research perspectives. A systematic review was conducted, analyzing the most relevant pathological conditions associated with iron metabolism, including iron overload and iron deficiency. Iron overload (IO) encompasses a wide range of disorders that lead to systemic iron accumulation and organ damage, while iron deficiency (ID) is characterized by insufficient iron availability for physiological needs. IO is dealt with a focused attention, exploring molecular mechanisms and emerging therapeutic strategies. In this context, hepcidin not only represents a valuable biomarker for iron overload but also serves as a potential target for novel therapies that are currently in the experimental phase. Conversely, for ID, both traditional biomarkers and recently proposed indicators help in diagnosing ID and correlating it with erythropoietic activity. Full article

Background and Objectives: Telemedicine has become an essential component of chronic Inflammatory Bowel Disease (IBD) care, yet the factors that shape patient satisfaction with remote consultations remain only partially understood. This study aimed to assess satisfaction with institutional telemedicine services among Italian patients with ulcerative colitis (UC) and Crohn’s disease (CD), and to identify sociodemographic, clinical and organisational predictors to inform more person-centred telehealth models. Materials and Methods: We conducted a prospective, multi-centre, cross-sectional study in three IBD units in northern, central and southern Italy between June and October 2024. Consecutive adult patients who had completed a scheduled, non-emergency telemedicine visit were invited within 24–48 h to complete an online questionnaire including the Italian Telemedicine Satisfaction Questionnaire (I-TSQ), sociodemographic items, IBD-related variables, and telemedicine process indicators (accessibility, technology usability, technical support, time saved). Data were analysed descriptively and with multivariable linear regression to determine independent predictors of satisfaction, adjusting for recruiting centre. Results: A total of 705 patients participated (54.9% UC; 55.3% disease duration > 10 years). Overall, telemedicine satisfaction was high (mean I-TSQ total 57.5 ± 4.9; range 35–70), and all respondents reported reduced indirect costs compared with in-person visits. Greater ease of technology use, more frequent contact with the care team, male sex, older age, and employment were independently associated with higher satisfaction scores. Conversely, first-ever teleconsultations, CD, subcutaneous therapies, more difficult platform access, and the need for technical support were linked to lower satisfaction. Model fit was modest (R² up to 0.20), suggesting the presence of additional unmeasured relational and contextual factors. Conclusions: Telemedicine for IBD is widely accepted in Italy, but satisfaction is strongly conditioned by digital usability, previous experience, and clinical complexity. Tailored telehealth pathways that incorporate user-friendly platforms, proactive technical support, and attention to vulnerable subgroups are needed to translate high satisfaction into sustained, equitable remote care. Full article

Nanoparticle-mediated photothermal conversion exploits the unique light-to-heat transduction properties of engineered nanomaterials to address challenges in energy, water, and healthcare. This review first examines fundamental mechanisms—localized surface plasmon resonance (LSPR) in plasmonic metals and broadband interband transitions in semiconductors—demonstrating how tailored nanoparticle compositions can achieve >96% absorption across 250–2500 nm and photothermal efficiencies exceeding 98% under one-sun illumination (1000 W·m⁻², AM 1.5G). Next, we highlight advances in solar steam generation and desalination: floating photothermal receivers on carbonized wood or hydrogels reach >95% efficiency in solar-to-vapor conversion and >2 kg·m⁻²·h⁻¹ evaporation rates; three-dimensional architectures recapture diffuse flux and ambient heat; and full-spectrum nanofluids (LaB₆, Au colloids) extend photothermal harvesting into portable, scalable designs. We then survey photothermal-enhanced thermal energy storage: metal-oxide–paraffin composites, core–shell phase-change material (PCM) nanocapsules, and MXene– polyethylene glycol—PEG—aerogels deliver >85% solar charging efficiencies, reduce supercooling, and improve thermal conductivity. In biomedicine, gold nanoshells, nanorods, and transition-metal dichalcogenide (TMDC) nanosheets enable deep-tissue photothermal therapy (PTT) with imaging guidance, achieving >94% tumor ablation in preclinical and pilot clinical studies. Multifunctional constructs combine PTT with chemotherapy, immunotherapy, or gene regulation, yielding synergistic tumor eradication and durable immune responses. Finally, we explore emerging opto-thermal nanobiosystems—light-triggered gene silencing in microalgae and poly(N-isopropylacrylamide) (PNIPAM)–gold nanoparticle (AuNP) membranes for microfluidic photothermal filtration and control—demonstrating how nanoscale heating enables remote, reversible biological and fluidic functions. We conclude by discussing challenges in scalable nanoparticle synthesis, stability, and integration, and outline future directions: multicomponent high-entropy alloys, modular photothermal–PCM devices, and opto-thermal control in synthetic biology. These interdisciplinary innovations promise sustainable solutions for global energy, water, and healthcare demands. Full article

This study presents a multifunctional theranostic platform based on anisotropic gold nanostars (AuNSs) functionalized with 2-thiouracil (2-TU) for cancer diagnostics and photothermal therapy (PTT). The unique plasmonic properties of AuNSs, combined with the anticancer and photothermal potential of 2-TU, were harnessed to create a system capable of simultaneous colorimetric biosensing and therapeutic action. Under dual-wavelength irradiation (660 nm and 525 nm), the AuNSs–2-TU conjugate demonstrated enhanced photothermal conversion efficiency, selective cancer cell targeting, and signal amplification, resulting in a significant reduction in the IC₅₀ for MCF-7 breast cancer cells. The system exhibited minimal cytotoxicity to normal fibroblasts (WS1), ensuring therapeutic precision. Compared to conventional spherical gold nanoparticles, this platform provides superior multifunctionality, including real-time biosensing with simple, naked-eye colorimetric readouts. These results highlight the potential of the AuNSs–2-TU conjugate as an innovative, minimally invasive nanotheranostic platform suitable for integrated cancer detection and treatment, particularly in resource-constrained settings. Full article

Background: Acinetobacter baumannii (AB), particularly carbapenem-resistant strains (CRAB), is a major cause of difficult-to-treat infections associated with substantial mortality. Contemporary data from Central and Eastern Europe remain scarce. We aimed to characterize the epidemiology, clinical features, and survival of patients with AB bloodstream infection in a multicenter Polish cohort. Methods: We conducted a retrospective multicenter study including consecutive adults with microbiologically confirmed AB bloodstream infection. Clinical and demographic data, comorbidities, infection origin, and antimicrobial treatments were collected. Outcomes included all-cause in-hospital mortality and infection-attributed mortality. Survival was assessed using Kaplan–Meier curves and log-rank tests, while factors associated with death were examined with univariable and multivariable Cox regression. Results: Among 245 patients with CRAB bloodstream infection, overall mortality was 69.4%, and infection-attributed mortality reached 51.8%. Most infections (75.1%) were hospital-acquired. In univariable analyses, male sex (HR = 0.66; p = 0.008) and colistin-based therapy (HR = 0.71; p = 0.037) were associated with improved survival. Conversely, hospital-acquired infection (HR = 0.43; p < 0.001) and acute kidney injury (HR = 1.40; p = 0.038) were linked to higher mortality. In the multivariable model, male sex remained protective (HR = 0.61; p = 0.006), while hospital-acquired infection (HR = 0.35; p < 0.001) and COVID-19 (HR = 1.64; p = 0.049) independently predicted death. After adjustment, no other comorbidities or antimicrobial regimens showed significant associations. Conclusions: In this multicenter cohort of patients with CRAB bloodstream infection, mortality remained extremely high. Hospital-acquired infection, acute kidney injury, and COVID-19 were strong independent predictors of poor outcomes, whereas male sex was associated with better survival. Although colistin-containing therapy appeared beneficial in univariable analysis, this effect did not persist after adjustment, underscoring potential confounding. These findings highlight the urgent need for early recognition, optimized antimicrobial strategies, and prevention of healthcare-associated spread to improve outcomes in CRAB bacteremia. Full article